PROJECT SUMMARY Identifying factors that influence age-related immune dysfunction (immunosenescence) in older adults is central to promoting well-being and reducing morbidity ? an increasing public health concern given the rapidly expanding aging population. Evidence from observational and experimental studies suggests that stress is associated with poorer immune function in older adults. However, less is known about the dynamic (intraindividual variability) emotional and physiological mechanisms by which stress influences older adults' immune function. In addition, emotion regulation may be a protective factor that can buffer stress-related immunosenescence in later life, but there is a dearth of knowledge in this area. This K99/R00 proposal lays the foundation for an independent research career focused on characterizing adaptive emotional and immunological mechanisms that contribute to healthy aging during stress. The proposed career development plan will provide the candidate: (1) expertise in theories and methodologies of aging research, (2) advanced knowledge in immunosenescence and age-related immune changes, and (3) training in emotion and emotion regulation processes focused specifically on contexts of aging and stress. The mentored phase capitalizes on substantial research and professional development resources at the University of Kentucky (UK) and the expertise of an inter-disciplinary mentoring team (UK: Dr. Segerstrom and Dr. Lutz; UC Berkeley: Dr. Mauss; Penn State University: Dr. Ram, UCLA: Dr. Effros). These experiences will supplement the candidate's existing background in stress, emotions, health, and quantitative methods. The present study has three aims to test different components of a proposed model. Aim 1 (K99): To examine whether emotion regulation moderates the association between life stressors and immunosenescence. Aim 2 (K99): To explain how daily stressors are associated with elevated stress biomarkers, through intraindividual variability in negative emotion. Aim 3 (R00): To test the moderated mediation pathways of the entire proposed biopsychosocial model. The research incorporates a rigorous approach to test the proposed model by examining its interacting components across different time domains (i.e., life stressors that occur over years and daily hassles that occur on a more micro level), in various samples (community-dwelling older adults and a large, nationally representative sample), and across several markers of immunosenescence (lymphocyte senescence, inflammation, a chief proinflammatory transcription factor, and a latent virus that may drive senescence). Concurrent and prospective lagged moderation and mediation models using multilevel modeling and regression will be used to test relationships among stressors, emotional and physiological responses to stress, immunosenescence, and emotion regulation. Ultimately, this project will increase understanding of the dynamic mechanisms by which stressors influence immunosenescence in older adults and the role of emotion regulation in promoting healthy aging.